Herbal Medicines Pregnancy and Lactation

Prévia do material em texto

Herbal Medicines in 
Pregnancy and Lactation
An Evidence-Based Approach
Edward Mills DPh MSc (Oxon)
Director, Division of Clinical Epidemiology
Canadian College of Naturopathic Medicine
North York, Ontario, Canada
Jean-Jacques Duguoa MSc (cand.) ND
Naturopathic Doctor
Toronto Western Hospital
Assistant Professor
Division of Clinical Epidemiology
Canadian College of Naturopathic Medicine
North York, Ontario, Canada
Dan Perri BScPharm MD MSc
Clinical Pharmacology Fellow
University of Toronto
Toronto, Ontario, Canada
Gideon Koren MD FACMT FRCP
Director of Motherisk
Professor of Medicine, Pediatrics and Pharmacology
University of Toronto
Toronto, Ontario, Canada
With a contribution from 
Paul Richard Saunders PhD ND DHANP
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© 2006 Taylor & Francis Medical, an imprint of the Taylor & Francis Group
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00 Prelims 1410 10/25/05 2:13 PM Page ii
CONTENTS
Preface v
Chapter 1 Traditional botanical medicines 1
Chapter 2 Pharmacognosy – the science of natural 
source medicines 9
Chapter 3 Methodology 21
Chapter 4 Herbal medicines 23
Chapter 5 Vitamins 301
Chapter 6 Supplements 325
Index 349
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PREFACE
Exposures to over-the-counter products are frequent in pregnant women. Perhaps
this is a paradoxical response to the decreased use of prescribed medications
during pregnancy for fear of teratogenicity. For many women, natural health
products such as herbal medicines or supplements may seem a reasonable alter-
native as the lay media often portrays natural medicines as safe. While the true
incidence of natural product use in pregnancy is not known, some studies suggest
that as high as sixty percent of pregnant women use natural therapies including
herbal medicines either during pregnancy or while planning.1 Pregnant women
often consider the use of natural products such as peppermint tea or ginger to
help with symptoms of pregnancy such as nausea and vomiting.2 In one study
of midwives practicing in North Carolina, half of the respondents admitted to
recommending herbal medicines to their patients for pregnancy related condi-
tions.3 Further to this intended use, it must be remembered that nearly half of
all pregnancies are unplanned and unexpected exposures to medicines and
supplements in the first trimester are not rare.
Despite the prevalent use of natural health products by pregnant women,
there is very little published evidence with regards to the safety and efficacy of
natural health products during pregnancy and lactation. Many modern and
classic texts warn against the use of natural product supplementation during
pregnancy or lactation for up to one-third of the products listed in their
monographs. However, most resources provide little information on the data
used to evaluate reproductive toxicity apart from reports of historical use of
herbs as abortifacients or uterine stimulants or animal data of genotoxicity or
teratogenicity. Data on efficacy during pregnancy is similarly scarce from
most texts.
To our knowledge, ours is the first text that aims to specifically address the
lack of data of natural health product use in pregnancy and lactation. While it
is not an exhaustive compendium of available supplements, it is a comprehen-
sive listing of common herbs, vitamins and supplements used by pregnant
women. Drawing on all available studies obtained through meta-analytic tech-
niques, we have graded the quality of evidence on natural product safety during
pregnancy and breastfeeding. Statements in traditional texts such as ‘use of this
herbal product should occur only after careful assessment of the benefits and
risks’ need clarification with up-to-date evidence from the medical literature.
Busy healthcare providers need to have access to quick and reliable information
they can use to help address patient concerns with regards to natural health
product use in pregnancy or lactation. We hope that this text will be received as
a valuable resource for all clinicians who treat pregnant patients. As natural
00 Prelims 1410 10/25/05 2:13 PM Page v
health supplements continue to gain popularity, we anticipate that the utility for
a text such as this will grow too. 
Jean-Jacques Duguoa
Edward Mills
Dan Perri
Gideon Koren
References
1. Maats FH, Crowther CA. Patterns of vitamin, mineral, and herbal supplementation
use prior to and during pregnancy. Aust NZ J Obstet Gynaecol 2002; 42:494–496.
2. Hollyer T, Boon H, Georgousis A, Smith M, Einarson A. The use of CAM by women
suffering from nausea and vomiting during pregnancy. BMC Complementary and
Alternative Medicine 2002; 2:5
3. Allaire AD, Moss M-K, Wells SR. Complementary and alternative medicine in
pregnancy: a survey of North Carolina certified nurse-midmives. Obstet Gynecol
2000; 95:19–23. 
vi Preface
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Chapter 1
TRADITIONAL BOTANICAL 
MEDICINES
Paul Richard Saunders
Introduction
Pregnancy and subsequent lactation have been an essential part of human exis-
tence for millennia, but unfortunately the experience has not been easy for all
women. Some of our earliest medicines were plants used to address the difficul-
ties and complications of these biologic processes and to better prepare the
expectant mother for pregnancy, delivery, and lactation. In many part of the
world women still use herbal medicines even when attended by Western medi-
cine.1,2 This short review from an historical perspective will first examine some
ofthe botanicals that have been used during pregnancy and delivery and then
during lactation. Reference will also be made to some of the scientific literature
on these botanical medicines.
Contraception and pregnancy
Although conception is a problem for some women, a more common problem is
contraception. In rural Mindanao (the Philippines) women still drink kamias and
other herbal preparations rather than use oral contraceptives.2 Quisumbing’s
thorough study of Philippine medicinal plants identified over 60 plants used as
abortifacients and over 130 plants used as emmenagogues.3 Of interest is
Kibatalia blancoi and K. gitingesis whose leaf and bark may have progesterone-
like effects.4,5 A 1995–1996 reproductive health survey of 6465 Paraguayan
women of reproductive age found they were most familiar (88%) with yuyos, a
variety of herbs usually drunk as a tea daily to prevent pregnancy.6 Studies in
India to find traditional, effective contraceptives have focused on Hibiscus rosa-
sinensis, Rudrapushpaka, Embelia ribes, Daucus carota, Butea monosperma,
Sapindus trifoliatus, Mentha arvensis, Ferula jaeschkeana, and several others
because of their anti-implantation activity.7 Herbs with potential as a male
contraceptive are Gossypium herbaceum and Tripterygium wilfordii.7
In traditional Chinese medicine, a core of 10–20 herbs is used in pregnancy.8
A review of traditional Chinese materia medica would, based on clinical tongue
and pulse diagnosis, include plants used for liver cleansing, blood regulating, qi
tonics, yin tonics and warming.9 Striga asiatica is one herb being studied as a
contraceptive.10
Moerman has published an exhaustive description of the plants used by
native North Americans; abortifacients number over 100 and female gynecol-
ogical aids nearly 350.11 A large number of these plants came to the knowledge
of European settlers by inquiry and observation with subsequent clinical use in
patients. When the outcome was repeatedly successful this was recorded and the
details of its use refined from repeated use by Eclectic physicians who
01 Chapter 1410 10/25/05 2:14 PM Page 1
differentiated between more effective and less well studied botanical medicines
in King’s American Dispensatory.12
Vitex agnus-castus has over a 2000-year history in female menstrual regula-
tion including infertility. It has also been shown to have beneficial effects for lac-
tation, making it in a sense a botanical alpha and omega of pregnancy and
lactation.13–15 Once the woman was pregnant Rubus idaeus leaf was used by the
Cherokee for labor pains and by the Cree and Cherokee to slow uterine bleed-
ing; benefits were attributed to its astringent and tannin properties.16,17 It is a
well-known partus preparator or parturient taken during pregnancy to tonify
the uterus, maintain pregnancy and ease delivery.18,19
One complication of pregnancy is threatened miscarriage. A well-known
herbal formula that prevents this is Viburnum prunifolium, Leonurus cardiaca,
and Mitchella repens.20 Viburnum prunifolium was used by the Delaware and
Micmac to strengthen and tone the uterus during pregnancy, and by the Eclec-
tics to calm uterine colic, for threatened miscarriage and painful uterine con-
tractions.21,22 L. cardiaca was regarded as a sedative for female nervousness and
hysteria, and for general female complaints by the Cherokee, Delaware, Iro-
quois, Micmac, Mohegan, and Shinnecock as well as by the Eclectics.23,24 M.
repens was used by the Cherokee, Delaware, Iroquois and Menominee for a
variety of complaints regarding the uterus.25 The Eclectics considered it one of
the most important herbs for successful pregnancy, to prevent miscarriage,
throughout the pregnancy for complications, and in the last weeks to ease deliv-
ery.26,27 This botanical formula was designed to address the uterine problems,
anxiety, nervousness, and pain that could accompany a possible miscarriage.
As the pregnancy neared completion a partus preparator was often given to
the expectant woman in the last 3–6 weeks to prepare the uterus for delivery and
reduce the pain of delivery. Botanicals drawn upon to affect the uterine circula-
tion and musculature included M. repens, V. prunifolium, Caulophyllum thalic-
troides, Actea (Cimicifuga) racemosa, Aralia nudicaulis, and for nervines
included those such as Leonurus cardiaca, Nepeta cataria, and Gelsemium sem-
pervirens.26,28,29 The dose of C. thalictroides was minimal before and during
labor to avoid fetal distress.29,30 Its Native American use related to pregnancy
and labor included the Cherokee, Menominee, Ojibwa, and Potawatomi.31 G.
sempervirens was used to calm the patient and help dilate the os in stalled
labor.32,33
The preferred botanical to address post-labor pains was G. sempervirens.32,33
Dose and timing were critical as administration too early or too frequent could
slow the labor process and too much after labor could make the woman too
drowsy to look after her newborn infant.32
Hemorrhage was the first severe complication after delivery as it could 
not only cause considerable blood loss and profound anemia, but also lead
to death if unchecked. Cinnamomum zeylanicum was a preferred anti-
hemorrhagic.28,34,35 It also provided some anti-microbial protection from puer-
peral fever, a important complication arising from infection contracted during
or after labor that took the life of many new mothers. C. zeylanicum is still used
2 Herbal medicines
01 Chapter 1410 10/25/05 2:14 PM Page 2
in traditional Chinese medicine for this type of fever.36 Other anti-hemorrhagics
included Capsella bursa-pastoris and Geranium maculatum whereas botanicals
preferred for post-partum anti-fever were Veratrum viride and Atropa
belladonna.37
In traditional Chinese medicine Angelica sinensis supplements blood, tones
the uterus and is often used throughout the pregnancy. Its stimulating or inhibit-
ing effect on the uterus is regulated by how long it is decocted in a larger for-
mula.38 In contrast, Western pharmacologists label it an abortifacient and
strongly recommend against its use in pregnancy.39 Rehmannia glutinosa is a
nutritive tonic that nourishes yin and blood and can be of benefit in bleeding,
Paeonia lactiflora can disperse blood thus controlling pain, and Cyperus rotun-
dus can control bleeding as well as antepartum and post-partum headache
pain.40 Three additional traditional Chinese medicinal herbs of note are Fritil-
laria cirrhosa for regulating uterine contractions and blood loss after labor, Pon-
cirus trifoliata to relieve pain and regulate uterine contractions, and
Codonopsis pilosula to build qi, address weakness, fatigue, and loss of appetite
– symptoms often present in the first trimester, near the end of pregnancy, or
after delivery.41
An indirect use of traditional Chinese medicinal herbs is moxibustion (char-
coal from Artemisia argyi and related species).42 In a randomized human study
it increased fetal activity during treatment and cephalic presentation after treat-
ment and at delivery.43 A study of recurrent spontaneous abortion using the tra-
ditional Chinese medicinal formula zhibai dihuang, with herbs to remove evil
heat, dampness, replenish blood and activate circulation, altered anti-ABO
group antibodies and yielded a high number of normal deliveries.44
Lactation
Mother’s breast milk is still regarded as best and in some settings is the infant’s
only chance for survival. A study of new mothers attending breast-feeding clin-
ics in Canada found up to 15% reported insufficient milk supply.45 No doubt
this has been a problem in some women, leading to efforts to identify herbal
remedies across a diversity of cultures. Brückner has reviewed the herbal drugs
most commonly used in Europe.46 Bingel and Farnsworth have produced the
most thorough review to date, identifying over 400 plants that have been used
ethnomedically and recorded in the literature as galactagogues.47 Not even 10%
of the plants have been studied scientifically so their individual mechanismand
effectiveness as galactagogues is generally unknown.
Breast pain, swelling, hardness, and even mastitis have been treated with
Phytolacca americana, Ricinus communis, and M. repens, all of which can be
applied topically before or between breast feeding. They must be cleansed from
the breast prior to nursing.48 A possible mechanism is their ability to facilitate
flow from the gland through the nipple and to the infant.47
In Central America, Mayan and other native women use a variety of herbs to
increase breast milk production. Coffea arabica and Camellia sinensis are two
diuretics that contain caffeine, and caffeine and theophylline, respectively, and
Traditional botanical medicines 3
01 Chapter 1410 10/25/05 2:14 PM Page 3
have been used – and shown experimentally – to promote lactation.47 Caffeine
in some infants can lead to insomnia and colic. Euphorbia lancifolia has been
used by humans for centuries and may also increase milk production in cows.49
Emotions such as fear and anxiety may reduce the release of milk suggesting
a role for herbs that reduce the psychological and physiological effects of emo-
tions.47 Lactuca virosa and L. sativa produce a dried sap used for sedation,
whereas L. biennis has been used to ease breast pain and promote lactation.50,51
Anethum graveolens is a sedative that has been used with some benefit.47,52 Seda-
tive plants often contain essential oils, compounds that dilate blood vessels,
relax muscles, and enhance sleep. Noteworthy are Origanum vulgare employed
in fomentations, Lavandula officinal, L. angustifolia, and L. vera that are added
to baths or applied locally for pain, and Mentha piperita, M. viridis, and
Nepeta cataria taken as an infusion.53
Beer, a well-known galactagogue, contains Humulus lupulus, noted for both
its sedative action and estrogenic effect on breast tissue, and Hordeum vulgare,
reputed to be galactogenic and to cause prolactin release.47,54 H. lupulus can be
applied to painful swellings such as of the breast, but is generally empirically
contraindicated in depression.55,56
Other galactagogues of note include Urtica dioica and U. urens which can be
applied topically or taken internally.57 Galega officinalis has enjoyed more pop-
ularity in its native Europe than North America for it ability to stimulate milk
production.58,59 Trigonella foenum-graecum has historically been widely used in
Europe and North Africa and some of the animal data are positive.60,61 Salvia
officinalis is used more as a lactation regulator, most often to reduce milk
production and pain when the baby has been weaned.62,63
Ayurveda, the traditional medicine of India, has yielded such galactagogues
as Rauwolfia serpentina, R. oreogiton, and R. volkensii, whose use is supported
by endocrinology and findings from clinical trials that have focused on its alka-
loid content. Reserpine, a dopamine-depleting agent can produce galactorrhea
in women and decrease anxiety, and several other alkaloids have similar activ-
ity.47 There is positive data for Leptadenia reticulata as well.47 Asparagus race-
mosus was examined in a clinical trial where it was used in a herbal formula
with six other herbs, but the results were not significant.64 Current and future
research could increase our knowledge about other herbs used traditionally in
rural India.65
Traditional Chinese medicinal botanicals for enhancing milk production in
humans include Astragalus membranaceus, Taraxacum mongolicum, Tetra-
panax papyrifera, Liquidambar taiwaniana, and Ligusticum chuaniong (L.
striatum) to name a few.66 In general these are qi, yin, and/or blood tonics.
Summary
The use of medicinal plants to address infertility, maintain pregnancy, ease the
birthing process, and aid in milk production or its cessation has been identified
in many cultures, several of whom have complex medical systems.1,2,4,6,9,11,65,67
Over 400 plants have been identified as ethnomedically affecting lactation.
4 Herbal medicines
01 Chapter 1410 10/25/05 2:14 PM Page 4
Unfortunately, modern science has not maintained pace in the study of the
mechanisms and relative benefit or potential harm of these plants. Women from
many cultural backgrounds continue to use plants despite the presence of mod-
ern medications. More detailed study in this area could yield new information
about mammalian reproductive endocrinology and physiology, plant pharma-
cognosy and constituent physiology, and identify the larger potential of at least
some of these plants.
References
1. Mabina MH, Moodley J, Pitsoe SB. The use of traditional herbal medication during
pregnancy. Trop Doct 1997; 27:84–86.
2. Quijano N Jr. Herbal contraceptives: exploring indigenous methods of family
planning. Initiatives Popul 1986; 8:22, 31–35.
3. Quisumbing E. Medicinal plants of the Philippines. Caloocan City, Philippines:
Katha Publishing, 1978:1079, 1110–1111.
4. Guerrero AM. Age-old methods of contraception. Initiatives Popul 1977; 3:20–25.
5. Quisumbing E. Medicinal plants of the Philippines. Caloocan City, Philippines:
Katha Publishing, 1978:729.
6. Bull SS, Melian M. Contraception and culture: the use of yuyos in Paraguay. Health
Care Women Int 1998; 19:49–60.
7. Chaudhery RR. The quest for a herbal contraceptive. Natl Med J India 1993;
6:199–201.
8. Wong HB. Effects of herbs and drugs during pregnancy and lactation. J Singapore
Paediatr Soc 1979; 21:169–178.
9. Hsu HY. Oriental materia medica: a concise guide. Long Beach, CA: Oriental
Healing Arts Institute, 1986:6–18.
10. Chaing HS, Merino-Chavez G, Yang LL, Wang FN, Hafez ES. Medicinal plants:
conception/contraception. Adv Contracept Deliv Syst 1994; 10:355–363.
11. Moerman DE. Native American ethnobotany. Portland, OR: Timber Press,
1998:765, 799–801.
12. Felter HW, Lloyd JU. King’s American Dispensatory, 18th ed, 1905. Reprinted, Sandy,
OR: Eclectic Medical Publications, 1983:iii–iv.
13. McCutcheon AR, Chastebarry IN, Chandler F, eds. Herbs everyday reference for
health professionals. Ottawa, ON: Canadian Pharmacists Association, Canadian
Medical Association, 2000:76–68.
14. Witman G, Gerhard I, Runnebaum B. The efficacy of the herbal drug Mastodynon
in femal infertility. Arch Gynecol Obstet 1993; 254:158–160.
15. Du Mee C. Vitex agnus castus. Aust J Herbal Med 1993; 5:63–65.
16. Moerman DE. Native American ethnobotany. Portland, OR: Timber Press,
1998:488–489.
17. Felter HW, Lloyd JU. King’s American Dispensatory, 18th ed, 1905. Reprinted.
Sandy, OR: Eclectic Medical Publications, 1983:1680–1683.
18. Scientific Committee. British herbal pharmacopoeia. Bournemouth, UK: British
Herbal Medicine Association, 1995:182.
19. Mitchell WA Jr. Plant medicine in practice using the teachings of John Bastyr. St.
Louis, MO: Elsevier Science, 2003:266.
20. Harper-Shove F. Prescriber and Clinical Repertory of Medicinal Herbs. Rustington,
Sussex, UK: Health Science Press, 1938:99.
Traditional botanical medicines 5
01 Chapter 1410 10/25/05 2:14 PM Page 5
21. Moerman DE. Native American Ethnobotany. Portland, OR: Timber Press,
1998:595.
22. Felter HW, Lloyd JU. King’s American Dispensatory, 18th ed, 1905. Reprinted. Sandy,
OR: Eclectic Medical Publications, 1983:2059–2062.
23. Moerman DE. Native American Ethnobotany. Portland, OR: Timber Press, 1998:301.
24. Felter HW, Lloyd JU. King’s American Dispensatory, 18th ed, 1905. Reprinted. Sandy,
OR: Eclectic Medical Publications, 1983:1125–1126.
25. Moerman DE. Native American Ethnobotany. Portland, OR: Timber Press,
1998:345–346.
26. Mitchell WA Jr. Plant medicine in practice using the teachings of John Bastyr. St.
Louis, MO: Elsevier Science, 2003:386.
27. Felter HW, Lloyd JU. King’s American Dispensatory, 18th ed, 1905. Reprinted. Sandy,
OR: Eclectic Medical Publications, 1983:1273–1274.
28. Harper-Shove F. Prescriber and clinical repertory of medicinal herbs. Rustington,
Sussex, UK: Health Science Press, 1938:103–104.
29. Felter HW, Lloyd JU. King’s American Dispensatory, 18th ed, 1905. Reprinted. Sandy,
OR: Eclectic MedicalPublications, 1983:468–472, 528–553, 916–923.
30. Wilson C. Useful Prescriptions. Cincinnati, OH: Lloyd Brothers Pharmacists, 1935:
102.
31. Moerman DE. Native American Ethnobotany. Portland, OR: Timber Press,
1998:144.
32. Felter HW, Lloyd JU. King’s American Dispensatory, 18th ed, 1905. Reprinted. Sandy,
OR: Eclectic Medical Publications, 1983:916–923.
33. Wilson C. Useful Prescriptions. Cincinnati, OH: Lloyd Brothers Pharmacists, 1935:
108.
34. Wilson C. Useful Prescriptions. Cincinnati, OH: Lloyd Brothers Pharmacists, 1935:
103.
35. Felter HW, Lloyd JU. King’s American Dispensatory, 18th ed, 1905. Reprinted. Sandy,
OR: Eclectic Medical Publications, 1983:557–560.
36. Hsu HY. Oriental materia medica a concise guide. Long Beach, CA: Oriental
Healing Arts Institute, 1986:375–376.
37. Felter HW, Lloyd JU. King’s American Dispensatory, 18th ed, 1905. Reprinted.
Sandy, OR: Eclectic Medical Publications, 1983:431–434, 927–929, 331–340,
2050–2054.
38. Hsu HY. Oriental materia medica a concise guide. Long Beach, CA: Oriental
Healing Arts Institute, 1986:540–542.
39. Barnes J, Anderson LA, Phillipson JD. Herbal medicines, 2nd ed. London, UK:
Pharmaceutical Press, 2002:47–50.
40. Hsu HY. Oriental materia medica a concise guide. Long Beach, CA: Oriental
Healing Arts Institute, 1986:148–149, 415–416, 546, 548–549.
41. Hsu HY. Oriental materia medica a concise guide. Long Beach, CA: Oriental
Healing Arts Institute, 1986:407–409, 526–527, 679–680.
42. Bensky D, Gamble A. Chinese herbal medicine: materia medica, 2nd ed. Seattle, WA:
Eastland Press, 1993:259–260.
43. Cardini F, Weixin H. Moxibustion for the correction of breech presentation: a
randomized controlled trial. JAMA 1998; 280:1580–1584.
44. Li DJ, Li CJ, Zhu Y. Treatment of integrated traditional and western medicine in
recurrent spontaneous abortion of immune abnormality type [English Abstract].
Zhongguo Zhong Xi YiJie He Za Zhi 1997; 17:390–392.
6 Herbal medicines
01 Chapter 1410 10/25/05 2:14 PM Page 6
45. MacIntosh HC. What is the pharmacological basis for the action of herbs that pro-
mote lactation and how can they best be utilized Part I. Can J Herbalism 2003;
XXIV:15–19, 36.
46. Brückner C. Anwendung and wert in europa gebräuchlicher lactationsördernder
heilpflanzen (galactagoga) [English Abstract]. Pädiatr Grenzgeb 1989;
28:403–410.
47. Bingel AS, Farnsworth NR. Higher plants as potential sources of galactagogues. In:
Wagner H, Farnsworth NR, eds. Economic and medicinal plant research volume 6.
London, UK: Academic Press, 1994:1–54.
48. Felter HW, Lloyd JU. King’s American Dispensatory, 18th ed, 1905. Reprinted.
Sandy, OR: Eclectic Medical Publications, 1983:1471–1475, 1380–1383,
1273–1274.
49. Rosengarten F Jr. A neglected Mayan galactagogue – ixbut (Euphorbia lancifolia). 
J Ethnopharmacol 1982; 5:91–112.
50. Felter HW, Lloyd JU. King’s American Dispensatory, 18th ed, 1905. Reprinted. Sandy,
OR: Eclectic Medical Publications, 1983:1114–1117.
51. Moerman DE. Native American Ethnobotany. Portland, OR: Timber Press,
1998:294.
52. Felter HW, Lloyd JU. King’s American Dispensatory, 18th ed, 1905. Reprinted. Sandy,
OR: Eclectic Medical Publications, 1983:203.
53. Felter HW, Lloyd JU. King’s American Dispensatory, 18th ed, 1905. Reprinted.
Sandy, OR: Eclectic Medical Publications, 1983:1420, 1123–1124, 1254–1256,
1252.
54. Felter HW, Lloyd JU. King’s American Dispensatory, 18th ed, 1905. Reprinted. Sandy,
OR: Eclectic Medical Publications, 1983:996–1000.
55. Felter HW, Lloyd JU. King’s American Dispensatory, 18th ed, 1905. Reprinted. Sandy,
OR: Eclectic Medical Publications, 1983:998–1000.
56. Brinker F. Herb Contraindications and Drug Interactions. Sandy, OR: Eclectic
Medical Publications, 2001:119.
57. Felter HW, Lloyd JU. King’s American Dispensatory, 18th ed, 1905. Reprinted. Sandy,
OR: Eclectic Medical Publications, 1983:2032–2034.
58. Felter HW, Lloyd JU. King’s American Dispensatory, 18th ed, 1905. Reprinted.
Sandy, OR: Eclectic Medical Publications, 1983:908.
59. Weiss RF. Herbal Medicine, 6th ed. Beaconsfield, UK: Beaconsfield Publishers,
1988:318.
60. Weiss RF. Herbal Medicine, 6th ed. Beaconsfield, UK: Beaconsfield Publishers,
1988:199, 336.
61. MacIntosh HC. What is the pharmacological basis for the action of herbs that pro-
mote lactation and how can they best be utilized part II. Can J Herbalism 2003;
XXV:15–11, 38.
62. Felter HW, Lloyd JU. King’s American Dispensatory, 18th ed, 1905. Reprinted.
Sandy, OR: Eclectic Medical Publications, 1983:1705–1706.
63. Weiss RF. Herbal medicine, 6th ed. Beaconsfield, UK: Beaconsfield Publishers,
1988:228.
64. Sharma S, Ramji S, Kumari S, Bapna JS. Randomized controlled trial of Asparagus
racemosus (Shatavari) as a lactogogue in lactational inadequacy. Indian Pediatr 1996;
33:675–677.
65. Anon. Learning from India’s traditional birth attendants, the dais. Arrows Change.
199; 5:3.
Traditional botanical medicines 7
01 Chapter 1410 10/25/05 2:14 PM Page 7
66. Hsu HY. Oriental Materia Medica a Concise Guide. Long Beach, CA: Oriental
Healing Arts Institute, 1986:521–523, 237–238, 311–312, 465, 446–447.
67. Raden-Sanusi HR, Werner R. The role of traditional healers in the provision of
health care and family planning services: Malay traditional and indigenous medi-
cine. Malays J Reprod Health 1985; 3(Suppl 1):S82–S89.
8 Herbal medicines
01 Chapter 1410 10/25/05 2:14 PM Page 8
Chapter 2
PHARMACOGNOSY – THE SCIENCE
OF NATURAL SOURCE MEDICINES
The study of medicinal plants and their properties is called pharmacognosy.
This science has led to the development of many drugs in use today including
aspirin (the basic salicylate structure was discovered from the white willow
while aspirin was synthesized from meadowsweet), opioids (originally from
opium poppies), the birth control pill (synthesized from steroid structures
found in a wild Mexican yam), and chemotherapeutic agents like vincristine
and vinblastine (from Madagascar periwinkle) or taxol (from the Pacific yew
tree).
Today, herbal medicine is big business. However, there is much confusion
about what herbal medicine is and is not. While pharmacognosy is a science
that deals with the discovery of medicines from natural substances, it is cer-
tainly not the same as herbalism. According to the American Society of Phar-
macognosy, its scope includes ‘the study of the physical, chemical, biochemical
and biological properties of drugs, drug substances, or potential drugs or drug
substances of natural origin as well as the search for new drugs from natural
sources. Research problems in pharmacognosy include studies in the areas of
phytochemistry, microbial chemistry, biosynthesis, biotransformation, chemo-
taxonomy, and other biological and chemical sciences’. The term herbalism
refers to a folk and traditional medicinal practice based on the use of plants and
plant extracts. In essence, herbalism is the practice of herb-based care and
pharmacognosy is the scientific study of herbs with medicinal purposes. Within
the practice of herbalism there are a variety of different traditions including, for
example, traditional Chinese medicine or the Indian ayurvedic medicine. Each
of these has a unique paradigm on health, illness, and disease. Unlike pharma-
cognosists, herbalists are not particularly interested in specific active con-
stituents found within a plant. Instead, they focus on the healing properties of
the plant or part of plant (seed, root, leaf, etc.) and how it will benefit the body
to heal itself. Although non-herbalists may also use herbal medicines in their
clinical practice, they likely do so under a different health paradigm. Home-
opaths also have a holistic approach to health, but their material medica uses a
‘like cures like’ philosophy of treating patients with ultra-dilute formulations
unlikely to contain significant (if any) ‘active’ ingredient. Homeopathy, then, is
unlike herbal medicine, herbalism, or pharmacognosy. It has not been included
in this text.
The current trend innatural product use follows many different health para-
digms – some are popular because of their use in traditional Chinese medicine
or Ayurveda, some from the widespread use of herbal medicine in Europe, and
some due to increasing published studies on natural medicines, somewhat rep-
resentative of the renewed interest in pharmacognosy. So, irrespective of the
02 Chapter 1410 10/25/05 2:14 PM Page 9
particular health paradigm from which the natural health products summarized
in this text are derived, we will adopt the pharmacology perspective (or perhaps
in this case, pharmacognosy would be the more accurate term). As such, indi-
vidual constituents (chemical entities) of each natural product are discussed
with regard to their pharmacologic or toxicologic properties. Since this likely
represents a new vocabulary for most healthcare professionals, some common
classes of herbal constituents are described below.
Glossary of terms used in natural product pharmacology
(pharmacognosy)
A true understanding of the nature of plant constituents demands a solid foun-
dation in organic chemistry since many constituent names are based on the
compound’s chemical structure. An explanation of the structure–function rela-
tionship of plant constituents is beyond the scope of this text. Whenever possi-
ble, chemical constituents will be described here by their pharmacologic
function or unique physicochemical properties rather than their structural
forms. However, more often than not, the constituents derived from plants are
grouped according to their structural similarity rather than functional effect. In
these cases, the chemistry is simplified such that undergraduate level organic
chemistry knowledge will suffice. Further details can be found in the texts
recommended at the end of this chapter.
Alkaloids are chemicals formed from amino acids. True alkaloids contain a
heterocyclic ring structure containing nitrogen while proto alkaloids do not
have the nitrogen in the ring. Pseudo-alkaloids are related compounds that con-
tain a heterocyclic ring structure containing nitrogen but are not derived from
amino acids. Alkaloids are highly reactive substances with biologic activity in
low doses. In plants, most alkaloids (which are bases) form salts with acids.
Alkaloids may be monocyclic, bicylic, or polycylic. Alkaloids may occur as pyri-
dine-piperidines, tropanes, quinolines, isoquinolines, indoles, imidazoles,
steroidals, purine bases, and alkaloidal amines. Drug examples of alkaloids
include atropine, ipecac, nicotine, colchicine, caffeine, theophylline, quinine,
vinblastine, tubocurarine, reserpine, yohimbine, morphine, and the ergot alka-
loids. They are usually bitter-tasting white solids (although nicotine is a brown
liquid). Apart from their similar structural roots, alkaloids are not related and
thus do not necessarily share any pharmacologic properties.
Anthocyanins are plant pigments that strongly absorb in the ultraviolet (UV)
spectrum and thus have a role in attracting insects (by carnivorous plants or for
pollination purposes) as well as UV protection. Plants containing anthocyanins
can be of a variety of colors. They are usually red, purple, or blue but depend-
ing on their oxidation state may even be yellow or colorless. Over 300 different
anthocyanins have been identified in plants. They are one class of flavonoid
compounds that are very popular today due to their possible health benefits as
antioxidants. The most popular supplements are grape seed extract, pine bark
extract, and green tea. Anthocyanin-containing plants have also been used his-
torically as anti-inflammatories and for enhancing vision. Cranberries, bilber-
10 Herbal medicines
02 Chapter 1410 10/25/05 2:14 PM Page 10
ries, apples, eggplant, and radish all contain anthocyanins. Anthocyanins also
contribute to the color changes of leaves in autumn.
Anthraquinones have a three-ring structure and have been used for centuries
as purgatives and dyes. They are usually found in plants in a glycoside form 
(i.e. attached to sugar molecules). Anthraquinone laxatives irritate the bowel
wall, provoking increased muscle contractions and peristaltic movements.
Examples include senna, cascara sagrada, rhubarb, yellow dock, and aloe.
Anthraquinones may also have antiviral, antibacterial, and cytotoxic properties.
Coumarins are derived from cinnamic acid and are usually found in grasses
and the pea family (such as clover). Coumarins are responsible for the scent of
fresh cut grass. Dicumarol, the fermentation product of coumarin that is
thought to inhibit vitamin K effects on coagulation biosynthesis due to its sim-
ilarity in structure to vitamin K, is the anticoagulant from which warfarin was
synthesized. Many coumarins, if injected, are anticoagulants but most plant
coumarins are neutralized in the digestive tract and so have very little anticoag-
ulant effects when ingested. Derivatives of coumarins have antifungal properties
(like umbelliferone from the parsley family) and vascular tone effects (like
esculin from horse chestnut).
Pharmacognosy 11
R
R
R
OH
O
(�)
O
O
8
7
6
5
10
9
1
2
3
4
Figure 2.1 Basic structure of anthocyanins.
Figure 2.2 Basic structure of anthraquinones.
02 Chapter 1410 10/25/05 2:14 PM Page 11
Flavonoids are commonly found as pigments in flowering plants. Over 2000
different flavonoid compounds have been found in plants in either the free state
or as glycosides. They are polyphenolic compounds with a base structure that
consists of two aromatic rings joined with a three-carbon chain – the so-called
‘C6-C3-C6’ carbon skeleton. The three-carbon chain may be part of a more
complex structure including ringed moieties. The nature of the functional
groups at this central complex determines the subclass of flavonoids. Some
examples include flavones (such as apigenin found in celery and other herba-
ceous plants of the Labiatae, Umbelliferae, and Compositae families), flavonols
(found in woody flowering plants like quercitol or kaempferol from Sambucus
nigra), flavonones, and anthocyanins. Flavonoids found in colorful fruits and
vegetables have powerful antioxidant properties. Flavonoids are the reason why
green tea, grape seed extract and pine bark extract have been so popular over
the past few years.
Isoflavonoids are similar in structure to flavonoids but have one of their ben-
zene rings at a slightly different position. Unlike most flavonoids, isoflavonoids
are colorless and are limited to legume plants. Soy isoflavones are touted 
as agents that may lower low-density lipoprotein (LDL) cholesterol and
triglycerides as well as helping with menopausal symptoms and complications.
12 Herbal medicines
5 4
6 3
7
8
O O
C
C
C
A
B
2
3
4
5
6
2'
3'
4'
5'
6'
o 2' 3'
4'
5'6'
1
2
3
45
6
7
8
A C B
Figure 2.3 Basic structure of coumarins.
Figure 2.4 Two variants of the basic structure of flavanoids.
02 Chapter 1410 10/25/05 2:14 PM Page 12
Glucosinolates is a term often used to refer to a group of bound toxins such
as the cyanogenic and isothiocyanate glycosides. Some glycosides produce
hydrocyanic acid when hydrolyzed. These are referred to as cyanogenic glyco-
sides. Amygdalin, found in apricot pits and bitter almonds, or prunasin, found
in wild cherry bark, for example, are cyanogenic glycosides. The hydrolysis of
the glycoside sinigrin from plants in the mustard family leads to allyl isothio-
cyanate – mustard oil. Plants from the mustard family as well as the cyanogenic
glycosides have been used due to their anticarcinogenic properties. Laetrile
(amygdalin) was a very popular cancer remedy in the 1980s despite clinical evi-
dence of a lack of effect. Unfortunately, after pure amygdalin was banned,
patients tried ingesting large amounts of apricot kernels, which led to several
deaths because apricot kernels also contain an enzyme that hydrolyzes amyg-
dalin and releases cyanide. Subsequent research showed that amygdalin alone
can lead to cyanide poisoning.Glycosides are compounds that contain a carbohydrate (glycone) and non-
carbohydrate (aglycone) moiety joined by an acetal group. Although their chem-
ical names can be quite complex, they can be recognized from their trivial
names which are formed from the source plant name and the suffix ‘-in’ such as
salicin which is found in Salix (willow). Salicin is an alcohol glycoside found in
willow bark that yields salicyl alcohol when hydrolyzed. Salicin has anti-inflam-
matory properties probably due to its oxidation into salicylic acid. It is shown
here.
Pharmacognosy 13
B
BCA
O
O
O
O
2
3
Flavanone Isoflavone
2-Hydroxyisoflavanone
synthase and dehydratase
CH2OH
CH2OH
OH
OH
HOSalicin
OO
Figure 2.5 The conversion of flavonone to isoflavone.
Figure 2.6 Salicin, an example of an alcohol glycoside.
02 Chapter 1410 10/25/05 2:14 PM Page 13
Classification of glycosides is difficult since it can be done either by the sugar
or the non-sugar group or by pharmaceutic viewpoint. Glycosides are ubiqui-
tous within plants and their aglycone groups include, among others, tannins,
aldehydes, alcohols, saponins, anthraquinones, lactones, flavanols, phenols, and
isocyanates. The anthraquinones described earlier are found in plants as glyco-
sides. Glucosinolates, a form of glycoside toxin, are described above. Gluco-
vanillin is an aldehyde glycoside that is hydrolyzed to vanillin (an aldehyde) – the
principal flavoring constituent of vanilla. Uva ursi, or bearberry, has a long tra-
dition in folk medicine as a urinary antiseptic. Arbutin is a phenol glycoside
found in bearberry (a small evergreen shrub) that can be hydrolyzed to the phe-
nol hydroquinone – the agent that made arbutin a popular choice for urinary
tract infections prior to sulfa antibiotics. Today hydroquinone is commonly
used topically as a skin bleacher. The combination of sapogenin and a sugar
yields a saponin glycoside which is described below as saponin. Sapogenins have
steroid or triterpenoid aglycone structures. Cardiac glycosides, like digitoxin,
are an example of a sapogenin with a steroid aglycone. These are discussed in
greater detail under saponins.
Lignans are plant products formed by the coupling of two para-propylphenol
(phenylpropanoid) moieties at their b carbon atoms. The three structures below
represent different lignan skeletal types.
If the two C6C3 units (4) are linked by a b,b�-bond the parent structure lignane
(5) is used as the basis for naming the lignan.
14 Herbal medicines
(2)(1) (3)
O
O
(4) (5)
1
23 5 5'6 6'
4 4 4'
5 6 2 2'3 3'��
� 1 1'
7 7'
8 8'
9 9'
Figure 2.7 Three different skeletal structures of lignans.
Figure 2.8 b-b�-bond linkage of two C6C3 units to form a lignan (lignane).
02 Chapter 1410 10/25/05 2:14 PM Page 14
If the two C6C3 units (4) are linked by a bond other than a b,b�-bond the par-
ent structure, neolignane, is used as the basis for naming the neolignan such as
3,3�-neolignane shown below.
Lignans and neolignans play a role in plant defense as they have antimicro-
bial, antifungal, and insect repellant properties. Podophyllum is the dried rhi-
zome and roots of Podophyllum peltatum (also known as mayapple or
American mandrake). A resin from podophyllin (called podophyllotoxin) is a
lignan that is used topically in the treatment of warts due to its antimitotic
properties. The chemotherapeutic drug etoposide is a semisynthetic podophyl-
lotoxin derivative. Podophyllotoxin is also a potent purgative. Other lignans,
such as secoisolariciresinol, are considered to be phytoestrogens. Flaxseed has
become very popular as a natural product therapy in women’s health due to its
very high lignan content. Other benefits of flaxseed, such as its potential role in
lowering LDL cholesterol, are also attributed to its lignan content. Much of the
natural product lay literature incorrectly states that lignans are synonymous
with phytoestrogens. The chemical structures, and thus function, of lignans are
quite variable. As discussed here, podophyllotoxin, a prototypic lignan, is used
for papillomas and not as a phytoestrogen. It is shown here.
Pharmacognosy 15
9 9'
8 8'7 7'
6 6'
1 1'2 2'
5 4 4' 5'
3 3'
H
H
H
H
O
O
O
O
OMe
OMe
MeO
Figure 2.9 Non- b-b�-bond linkage of two C6C3 units to form a neolignan (3,3’-
neolignane).
Figure 2.10 Podophyllotoxin, an example of a lignan.
02 Chapter 1410 10/25/05 2:14 PM Page 15
Saponins are compounds that form colloidal solutions in water and foam on
shaking. The name comes from the soapwort plant (Saponaria) the root of
which was used as a soap. They consist of a polycyclic aglycone derived from
squalene that is either a choline steroid or a cyclic triterpenoid (see terpenoids
for description) attached via C3 and an ether bond to a sugar side chain, thus
making them glycosides. Certain saponins called ‘sapotoxins’ are used as fish
poisons. They have even been used in poison arrow tips. When ingested,
saponins are usually safe in humans; however, when injected, their detergent
effect on the lipid cell membrane leads to hemolysis. A large variety of plants
contain saponins. The physiologic effects of saponins depend on the particular
aglycone. Saponins from wild yam or fenugreek are precursors to estrogens or
progestogens. They also exert lipid-lowering effects. The cardiac glycosides, like
digitoxigenin from the foxglove plant, have a steroid aglycone group. These
agents enhance cardiac contractility by increasing intracellular myocyte calcium
concentration through effects on the Na�/K� ATPase pump. Many plants have
cardiac glycosides including lily-of-the-valley, Christmas rose, oleander, squill,
and ouabain. Glycyrrhizin is a saponin from licorice that has been used as an
expectorant and sweetener. When it is hydrolyzed in the body it forms gly-
cyrrhetinic acid which inhibits enzymes that metabolize prostaglandins E2 and
F2a. Physiologically, this leads to a reduction in gastric acid secretion and stim-
ulation of uterine smooth muscle. A metabolite of glycyrrhetinic acid can
inhibit 11-b-hydroxysteroid dehydrogenase which converts active cortisol to
inactive cortisone in the kidneys. The net effect is sodium and water retention,
hypokalemia, and hypertension. Ginseng contains a mixture of triterpenoid
saponins, several of which are steroidal triterpenes called ginsenosides. These
are thought to be responsible for ginseng’s biologic properties. The skeleton
structure for the triterpenoid saponins of ginseng (ginsenosides) is shown
below.
Tannins are plant polyphenols that contain hydroxyl or carboxyl groups that
can form strong complexes with proteins. The ability of tannins to precipitate
16 Herbal medicines
R2O
OR1
OR2
2OS
2OR
HO
12
3
6
HO
Figure 2.11 Typical skeletal structure of triterpenoid saponins found in ginseng
(ginsenosides).
02 Chapter 1410 10/25/05 2:14 PM Page 16
proteins enables the conversion of animal hides to leather. Tannins are also
responsible for the ‘puckering’ taste of red wine or unripe fruit. Tannins are
broadly categorized into two forms – hydrolyzable and non-hydrolyzable.
Hydrolyzable tannins have a polyol (like D-glucose) central core and hydroxyl
groups that are esterified with phenolic compounds. Hydrolyzable tannins are
usually present in low amounts in plants. Tannins can combine with proteins
and make them resistant to proteolytic enzymes. When used in living tissues this
action is referred to as an ‘astringent’ effect. Astringents have historically been
applied topically to burns and wounds or taken internally for gastrointestinal
tract disorders like ulcers or gastritis. When superficial proteins in exposed tis-
sues are precipitated, a protective and mildly antiseptic coat is thought to form
that enables regeneration of tissue to occur below. The astringent effects of tan-
nins from witch hazel leaves or nutgall have been known for centuries. A typi-
cal polymer of gallic acid is shown below. Tannic acid is a polymer of about
eight monomers of gallic acidand glucose.
Non-hydrolyzable tannins (also called condensed tannins based on their
small molecular size) are composed of flavonoid units linked by carbon-to-
carbon bonds that cannot be cleaved by hydrolysis. When non-hydrolyzable tan-
nins are heated in acidic solutions they form anthocyanidin pigments (described
earlier) leading to their other synonym, proanthocyanidins. Proanthocyanidins
(also referred to as pycnogenols) lead to anthocyanidins that are effective
antioxidants and free radical scavengers. As discussed earlier, they are found in
pine bark, grape seed, and green tea. A trimer of catechin is shown here.
Pharmacognosy 17
HO
HO
HO
HO
HO
HO
HO Glucose moiety
OH
OH
OH
OH
OH
OH
O
O
O-C
O - CO
CO - CH2
CO - O
Figure 2.12 Structure of a hydrolyzable tannin formed as a polymer of gallic acid with
a polyol (glucose moiety) at the core.
02 Chapter 1410 10/25/05 2:14 PM Page 17
Terpenes and terpenoids are synthesized from a 5-carbon isoprene molecule
(C5H8). Terpenes are hydrocarbons and terpenoids are oxygen-containing
hydrocarbons. Since all these molecules are made from isoprene, they can also
be called isoprenoids. Two isoprene units form a 10-carbon molecule called a
monoterpene. Terpenoids can be classified based on the number of isoprene units
(hence carbons) that make up their skeleton structure. These are summarized in
the table below:
A subgroup of structurally related sesquiterpenes are limited to only few fam-
ilies of plants such as Asteraceae. These are called sesquiterpene lactones and usu-
ally are responsible for the bitter taste and toxicity of many plants in which they
are found. Artemisinin, a sesquiterpene lactone from Artemisia annua has a long
history of use for its antimalarial properties. Parthenolide is a sesquiterpene
lactone found in feverfew which has been shown to reduce the frequency and
severity of migraine. Many triterpenoids exist as pentacyclic structures resem-
bling steroid skeletons. Others have a tetracyclic structure. Since most are alcohols
they can combine with sugars to form glycosides. Pentacyclic triterpenoids are
often saponins. Carotenoids are found in brightly colored fruits and vegetables.
Lycopene and other carotenoids are powerful antioxidants.
18 Herbal medicines
HO
HO
HO
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
O
O
O
Terpenoid Isoprenes Formula Example
Monoterpenoids 2 C10H16 Cineole (found in eucalyptus)
Sesquiterpenoids 3 C15H24 Valerenic acid (found in valerian)
Diterpenoids 4 C20H32 Taxol (from Pacific yew)
Triterpenoids 6 C30H48 Glycyrrhetic acid (from licorice)
Tetraterpenoids 8 C40H60 Lycopene (carotenoids)
Figure 2.13 Structure of a non-hydrolyzable tannin formed as a trimer of catechin
without a polyol at its core.
Table 2.1 Nomenclature of terpenoids
02 Chapter 1410 10/25/05 2:14 PM Page 18
Volatile oils are the fragrant or aromatic plant compounds that evaporate
when exposed to air at normal temperatures. They are also called essential oils
as these oils impart the odoriferous character or ‘essence’ of the plant. Spices
are made from plant parts that contain volatile oils. Volatile oils are also used
in aromatherapy, as flavoring agents, and in the perfume industry. Volatile oils
may also have medical properties such as the antiseptic or expectorant proper-
ties of eucalyptus oil or disinfectant properties such as pine oil. Structurally,
volatile oils are either terpenoid derivatives (like those volatile oils characteris-
tic of menthol, camphor, lemon and pine) or phenylpropanoids (like those in
cinnamon, cloves, and wintergreen).
Pharmacognosy 19
H3C
CH3
CH3
H
H
O
O
O
OO
H H
O
O
O
Figure 2.14 Artemisinin, a sesquiterpene lactone with antimalarial properties.
Figure 2.15 Parthenolide, a sesquiterpene lactone found in feverfew.
CH3
CH3H3C
HO
H
Figure 2.16 Menthol, a volatile oil and terpenoid derivative.
02 Chapter 1410 10/25/05 2:14 PM Page 19
Suggested reading
Bisset NG, Wichtl M, eds. Herbal Drugs and Phytopharmaceuticals. Boca Raton: CRC
Press, 1994.
Bruneton J. Pharmacognosy: Phytochemistry Medicinal Plants, 2nd ed. Hampshire, UK:
Intercept, 1999.
Dewick PM. Medicinal Natural Products: A Biosynthetic Approach. Chichester: John
Wiley and Sons, 1997.
Evans WC. Trease and Evans Pharmacognosy, 14th ed. London: WB Saunders Company
Ltd, 1996.
Heinrich M, Barnes J, Gibbons S, Williamson EM. Fundamentals of Pharmacognosy
and Phytotherapy. Edinburgh: Churchill Livingstone, 2004.
Huang KC. The Pharmacology of Chinese herbs, 2nd ed. Boca Raton: CRC Press, 1999.
Robbers JE, Speedie MK, Tyler VE. Pharmacognosy and Pharmacobiotechnology.
Baltimore: Williams and Wilkins, 1996.
20 Herbal medicines
OH
OCH3
Figure 2.17 Eugenol (from cloves)
02 Chapter 1410 10/25/05 2:14 PM Page 20
Chapter 3
METHODOLOGY
In keeping with the principles of evidence-based practice, we have endeavored
to identify all the relevant literature on the specific health products examined.
Our search strategy employed systematic searching of the following databases:
● AltHealthWatch
● AMED
● CinAhl
● Cochrane Database of Systematic Reviews
● Cochrane CENTRAL Controlled Trials Database
● E-Psyche
● DARE
● MedLine
The MeSH terms used for searching included ‘pregnancy’, ‘lactation’, and
‘breastfeeding’. For individual health products, we searched using both the com-
mon and Latin names, and where appropriate, we searched using known syn-
onyms. In the case of a well-known active ingredient or constituent, this term
was also used in the search for its safety during pregnancy and lactation. The
principal databases used were:
● Pubmed
● Cochrane Trial Registry (CENTRAL) and Cochrane Review database
● AMED
● CINAHL
● E-Psyche
To ensure that reports, trials, and other forms of evidence were not overlooked
owing to the variety of common names for each individual herb, e.g. Panax gin-
seng is also known as ren shen in traditional Chinese medicine, the following
additional databases were consulted:
● www.naturalstandard.com
● www.naturaldatabase.com
● The Complete German Commission E Monographs by the American
Botanical Council
Each relevant journal article was collected and referenced in our database. The
nature of the findings and the grade of evidence were then assessed and
compiled in our final report.
03 Chapter 1410 10/25/05 2:14 PM Page 21
The grade of evidence for indications was evaluated as follows:
The level of evidence for harm was evaluated as follows:
22 Herbal medicines
Grade Level of evidence
A Very strong scientific evidence
Statistically significant evidence of benefit from one or more systematic
reviews or meta-analyses
B1 Strong scientific evidence
Statistically significant evidence of benefit from one or more properly
conducted randomized controlled trials (RCTs).
B2 Good scientific evidence
Statistically significant evidence of benefit from one or more RCTs. The
RCTs, however, are either of small sample size or have discrepancies in their
methodologies
C Fair scientific evidence
Statistically significant evidence of benefit from one or more cohort studies or
outcome studies
D Weak scientific evidence
Evidence from case series
E Theoretical and/or clinical evidence
Evidence from case reports or expert opinion or laboratory studies
F Historical or traditional evidence
Historical or traditional evidence of use by medical professionals,
herbologists, scientists or aboriginal groups
Level Evidence
1a Very strong scientific evidence
Statistically significant evidence from one or more systematic reviews or
RCTs
1b Strong scientific evidence
Statistically significant evidence from one or more cohort studies or control
studies
1c Good scientific evidence
Evidence from one or more case series
2 Fair scientific evidence
Evidence based on case reports
3 In vitro scientific evidence
Evidence based on scientific studies conducted on animals, insects or
microorganisms, or laboratory studies on human cells
4 Theoretical evidence
Evidence based on scientifictheory or expert opinion
5 Unknown
No available information
03 Chapter 1410 10/25/05 2:14 PM Page 22
Chapter 4
HERBAL MEDICINES
Herbal medicines are increasingly popular among the general public, particu-
larly women of childbearing age. These medicines are not only viewed as hav-
ing clinical benefits but are also generally believed to be safe. In some cases, a
systematic review of the evidence-based medicine literature shows that this is
not the case.
In pregnancy, soon-to-be mothers are concerned about all medications that
may affect their health, the health of their fetus, and the pregnancy outcome.
When it comes to the types of evidence for herbal medicines during pregnancy
and lactation, not all evidence is created equally. The type of evidence for the
safety of herbal medicines during pregnancy and lactation ranges from
theoretical to animal studies, to case reports, to cohort studies and finally to
randomized controlled trials.
This chapter aims to provide healthcare practitioners and mothers-to-be with
the best available evidence-based safety information on the products they may
choose to use or not to use during pregnancy and lactation. We selected 60
herbal medicines in total. In choosing these herbs, we set forth a number of
selection criteria. These are outlined below.
Herbs that are frequently used during pregnancy, e.g. black and blue cohosh,
red raspberry, evening primrose oil
Herbs that are used to treat pregnancy-related complaints, e.g. ginger
Herbs that are known abortifacients, e.g. pennyroyal, parsley
Herbs that have narrow therapeutic indices and are toxic, e.g. digitalis, deadly
nightshade, ephedra
Herbs that are used more often by women than men, e.g. red clover, don quai
Herbs that are known to have hormonal effects, e.g. chastetree
The most frequently used herbs, e.g. St. John’s wort (depression), garlic (hyper-
lipidemia), ginkgo (memory), Echinacea (immune system)
Systematic reviews on all 60 herbal medicines are presented as follows:
Common name
The name by which the herb is commonly referred to, e.g. garlic.
Latin name
The Latin name (genus, species) of the herb, e.g. Allium sativum. In some cases,
more than one species of the herb has the same therapeutic effect, e.g. Panax spp.
04 Chapter 1410 10/25/05 2:15 PM Page 23
Synonyms
Other names by which the herb may be known.
Indications
The main therapeutic indications for the herb. According to evidence-based
medicine principles, the indications for the herb are evaluated based on grades/
levels of evidence (see Chapter 3).
Pregnancy
The safety of the herb during pregnancy. According to evidence-based medicine
principles, the safety of the herb during pregnancy is evaluated based on
grades/levels of evidence (see Chapter 3).
Lactation
The safety of the herb during lactation. According to evidence-based medicine
principles, the safety of the herb during lactation is evaluated based on grades/
levels of evidence (see Chapter 3).
Contraindications
Conditions and diseases in which the herb should not be taken.
Caution
Conditions or diseases in which the herb should be used with caution.
Constituents
The main pharmacological constituents in the herb.
Toxicity
The toxicity of the herb (lethal dose (LD50) where available).
Pharmacology
General pharmacological properties of the herb.
Drug interactions
Drugs that may interact with the herb.
Parts used
The part that provides the therapeutic benefits of the herb, e.g. root, leaf, stem.
24 Herbal medicines
04 Chapter 1410 10/25/05 2:15 PM Page 24
ALFALFA
Medicago sativa
Synonyms/common names/related compounds1
Feuille de luzerne, lucerne, medicago, phytoestrogen, purple medick
Indications
Menopausal symptoms (with sage):2 Evidence grade B2
Elevated cholesterol:3–5 Evidence grade D
Atherosclerosis:6,7 Evidence grade E
Diabetes:8,9 Evidence grade E
Pregnancy
Estrogenic activity:10–13 Evidence level 3
A study on the effects of dietary genistein exposure during development found
that dietary genistein produced effects in multiple estrogen-sensitive tissues in
both male and female rats.10 Another study reported estrogenic activity of
genistein and daidzein in human cells in vitro and in rats.11 The phytoestrogen
coumestrol, contained in alfalfa, was reported to be 35 times more potent than
the phytoestrogens genistein, biochanin A, formononetin and daidzein.12 A
review article on the potential value of plants as sources of anti-fertility agents
reported that alfalfa has estrogenic activity.13
Isolated compounds have uterine-stimulating activity:14 Evidence level 4
A review article on the potential value of plants as sources of anti-fertility
agents reported that alfalfa was a uterine stimulant and that its constituent
stachydrine was a uterine stimulant.14
Emmenagogue:15 Evidence level 4
A herbal medicine compendium reported that alfalfa is an emmenagogue.15 There
are no reports in the scientific literature of alfalfa being an emmenagogue.
Anti-gonadotrophic activity:14 Evidence level 4
A review article on the potential value of plants as sources of anti-fertility
agents reported that alfalfa had anti-gonadotrophic activity in rats where the
acid extract interfered with the growth of the seminal vesicles and potentiated
the action of estrogens.14
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04 Chapter 1410 10/25/05 2:15 PM Page 25
Consumed as food
Minimal risk:15–18 Evidence level 3
In a study on the effects of alfalfa feeding on pregnancy and lactation in beef
heifers, no adverse effects were reported when alfalfa was consumed in food
amounts.16 A herbal medicine compendium reported that when consumed as
food, alfalfa is believed to be of minimal risk.15
Lactation
Estrogenic activity:10–12 Evidence level 3
A study on the effects of dietary genistein exposure during development found
that dietary genistein produced effects in multiple estrogen-sensitive tissues in
both male and female rats.10 Another study reported estrogenic activity of
genistein and diadzein in human cells in vitro and in rats.11 The phytoestrogen
coumestrol, contained in alfalfa, was reported to be 35 times more potent than
the phytoestrogens genistein, biochanin A, formononetin and daidzein.12
Lactogenic:14 Evidence level 4
A review article on the potential value of plants as sources of anti-fertility
agents reported that alfalfa seeds may be lactogenic.14
Consumed as food
Minimal risk:15–17 Evidence level 3
In a study on the effects of alfalfa feeding on pregnancy and lactation in beef
heifers, no adverse effects were reported with alfalfa consumed in food
amounts.16 A herbal medicine compendium reported that when consumed as
food, alfalfa is believed to be of minimal risk.15
Contraindications
Systemic lupus erythematosus19,20
Caution
● Hormone sensitive conditions such as breast, uterine, or ovarian cancer,
endometriosis and fibroids12,21
● Diabetes 15
Constituents
● Saponins15,22
● Flavonoids23
● Phytoestrogens:1,12,24 coumestrol, genistein, biochanin A, and daidzein
● Vitamins A, C, E, and K15
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04 Chapter 1410 10/25/05 2:15 PM Page 26
● Manganese15,25
● Stachydrine14
Toxicity
In a 6-week study, no signs of toxicity were reported in six humans consuming
160 g a day of alfalfa for 3 weeks followed by 80 g of alfalfa a day for 3 weeks.5
Pharmacology
● The phytoestrogens coumetrol, genistein, biochanin A and daidzein have
been shown to have estrogenic properties.10–12,24
● The saponin constituents in alfalfa leaves were shown to decrease total
cholesterol levels without affecting high-density lipoprotein levels.15
● Alfalfa constituents may decrease cholesterol absorption and increase fecal
excretion of neutral steroids and bile acids.15,26
● Alfalfa contains manganese which might be responsible for its hypoglycemic
effects.15
● Alfalfa contains medicagol, which appears to have anti-fungal properties.1
Drug interactions1
Anti-coagulants15
Photosensitizing drugs27
Oral contraceptives1,15
Hormone therapy15
Warfarin (Coumadin)15Parts used
Above ground parts28
References
1. Jellin JM, Batz F, Hitchens K. Natural Medicines Comprehensive Database, 3rd ed.
Stockton, CA: Therapeutic Research Faculty, 2002:1530.
2. De Leo V, Lanzetta D, Cazzavacca R, Morgante G. [Treatment of neurovegetative
menopausal symptoms with a phytotherapeutic agent]. Minerva Ginecol 1998;
50:207–211.
3. Malinow MR, Connor WE, McLaughlin P et al. Cholesterol and bile acid balance in
Macaca fascicularis. Effects of alfalfa saponins. J Clin Invest 1981; 67:156–162.
4. Molgaard J, von Schenck H, Olsson AG. Alfalfa seeds lower low density lipoprotein
cholesterol and apolipoprotein B concentrations in patients with type II hyperlipo-
proteinemia. Atherosclerosis 1987; 65:173–179.
5. Malinow MR, McLaughlin P, Stafford C. Alfalfa seeds: effects on cholesterol metabolism.
Experientia 1980; 36:562–564.
6. Malinow MR. Experimental models of atherosclerosis regression. Atherosclerosis
1983; 48:105–118.
7. Malinow MR, McLaughlin P, Naito HK, Lewis LA, McNulty WP. Effect of alfalfa
meal on shrinkage (regression) of atherosclerotic plaques during cholesterol feeding
in monkeys. Atherosclerosis 1978; 30:27–43.
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8. Swanston-Flatt SK, Day C, Bailey CJ, Flatt PR. Traditional plant treatments for
diabetes. Studies in normal and streptozotocin diabetic mice. Diabetologia 1990;
33:462–464.
9. Gray AM, Flatt PR. Pancreatic and extra-pancreatic effects of the traditional anti-
diabetic plant, Medicago sativa (lucerne). Br J Nutr 1997; 78:325–334.
10. Delclos KB, Bucci TJ, Lomax LG et al. Effects of dietary genistein exposure during
development on male and female CD (Sprague-Dawley) rats. Reprod Toxicol 2001;
15:647–663.
11. Casanova M, You L, Gaido KW et al. Developmental effects of dietary phyto-
estrogens in Sprague-Dawley rats and interactions of genistein and daidzein with rat
estrogen receptors alpha and beta in vitro. Toxicol Sci 1999; 51:236–244.
12. Elakovich SD, Hampton JM. Analysis of coumestrol, a phytoestrogen, in alfalfa
tablets sold for human consumption. J Agric Food Chem 1984; 32:173–175.
13. Farnsworth NR, Bingel AS, Cordell GA, Crane FA, Fong HH. Potential value of
plants as sources of new anti-fertility agents II. Pharm Sci 1975; 64:717–753.
14. Farnsworth NR, Bingel AS, Cordell GA, Crane FA, Fong HH. Potential value of
plants as sources of new anti-fertility agents I. J Pharm Sci 1975; 64:535–598.
15. Newall CA, Anderson LA, Phillipson JD. Herbal Medicines: A Guide for Health-care
Professionals. London, UK: Pharmaceutical Press, 1996:296.
16. Vanzant ES, Cochran RC, Johnson DE. Pregnancy and lactation in beef heifers graz-
ing tallgrass prairie in the winter: influence on intake, forage utilization, and grazing
behavior. J Anim Sci 1991; 69:3027–3038.
17. Coffey KP, Paterson JA, Saul CS et al. The influence of pregnancy and source of
supplemental protein on intake, digestive kinetics and amino acid absorption by
ewes. J Anim Sci 1989; 67:1805–1814.
18. Guay KA, Brady HA, Allen VG et al. Matua bromegrass hay for mares in gestation
and lactation. J Anim Sci 2002; 80:2960–2966.
19. Malinow MR, Bardana EJ Jr, Pirofsky B, Craig S, McLaughlin P. Systemic lupus
erythmatosus-like syndrome in monkeys fed alfalfa sprouts: role of a nonprotein
amino acid. Science 1982; 216:415.
20. Roberts JL, Hayashi JA. Exacerbation of SLE associated with alfalfa ingestion. 
N Engl J Med 1983; 308:1361.
21. Kurzer MS, Xu X. Dietary phytoestrogens. Annu Rev Nutr 1997; 17:353–381.
22. Malinow MR, McLaughlin P, Stafford C et al. Comparative effects of alfalfa
saponins and alfalfa fiber on cholesterol absorption in rats. Am J Clin Nutr 1979;
32:1810–1812.
23. Stochmal A, Piacente S, Pizza C et al. Alfalfa (Medicago sativa L.) flavonoids. 1.
Apigenin and luteolin glycosides from aerial parts. J Agric Food Chem 2001;
49:753–758.
24. Leung AY, Foster S. Encyclopedia of Common Natural Ingredients Used in Food,
Drugs and Cosmetics. New York, NY: John Wiley & Sons, 1996:649.
25. Rubenstein AH, Levin NW, Elliott GA. Manganese-induced hypoglycemia. Lancet
1962:1348–1351.
26. The Review of Natural Products by Facts and Comparisons. St. Louis, MO: Wolters
Kluwer Co., 1999.
27. Brown R. Potential interactions of herbal medicines with anti-psychotics, anti-
depressants and hypnotics. Eur J Herbal Med 1997; 3:25–28.
28. Brinker F. Herb Contraindications and Drug Interactions. Sandy, OR: Eclectic
Medical Publications, 2001:432.
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04 Chapter 1410 10/25/05 2:15 PM Page 28
ALOE
Aloe spp.
Synonyms/common names/related substances1
A. vera (A. barbadensis), A. ferox, A. africana, A. arborescens natalenis, A.
capensis, A. leaf gel, A. perfoliata, A. perryi, A. spicata, salvia, cape aloes,
Barbados aloe, Curacao aloe, hepatic aloes, aloe dried juice from leaf, aloe
juice, burn plant, elephant’s gall, hsiang-dan, lily of the desert, lu-hui, miracle
plant, plant of immortality
Indications
Oral
Chronic constipation:2–6 Evidence grade B1
Solid tumors (with melatonin):7 Evidence grade C
Elevated cholesterol and triglycerides, hyperglycemia Evidence grade C
and low high-density lipoprotein cholesterol 
(with husk of Isabgol):8
Chronic venous leg ulcers:9 Evidence grade C
Fibromyalgia, chronic fatigue syndrome:10 Evidence grade C
Diabetes type 2:11–13 Evidence grade E
Bronchial asthma (aloe vera gel):14 Evidence grade E
Topical
Psoriasis vulgaris:15 Evidence grade B1
Herpes simplex type II:16,17 Evidence grade B1
Seborrheic dermatitis:18 Evidence grade B1
Radiation induced dermatitis:19 Evidence grade B2
Occupational dry skin, irritant contact dermatitis:20 Evidence grade B2
Burn wounds:21 Evidence grade C
Alveolar osteitis:22 Evidence grade C
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04 Chapter 1410 10/25/05 2:15 PM Page 29
Chronic venous leg ulcers:9 Evidence grade C
Anti-arthritic, anti-inflammatory (A. africana):23 Evidence grade E
Anti-inflammatory (A. vera):24 Evidence grade E
Wounds (A. vera):24,25 Evidence grade E 
Pregnancy
Oral
Potentially nephrotoxic:26 Evidence level 2
Potential hepatic dysfunction:26 Evidence level 2
A case of acute oliguric renal failure and liver dysfunction was reported in the
literature following traditional therapeutic use of cape aloes.26
Potential abortifacient:27 Evidence level 4
Emmenagogue:27 Evidence level 4
A review article on the potential value of plants as sources of anti-fertility agents
reported that aloe species are potential abortifacients and emmenagogues.27
Potentially genotoxic:3,28,29 Evidence level 3
Potentially mutagenic:3,28,29 Evidence level 3
Potentially carcinogenic:3,28,29 Evidence level 3
Aloe-emodin, a 1,8-dihydroxyanthraquinone found in aloe, is potentially
carcinogenic, mutagenic and genotoxic in mice.3,28,29
Topical
Aloe vera gel – minimal risk:3,30 Evidence level 4
A herbal medicine compendium reported that the external use of aloe vera gel
is not a concern during pregnancy. The external use of aloe was not reported in
the scientific literature as contraindicated or safe during pregnancy or lactation.
Lactation
Oral
Potentially genotoxic:3,28,29 Evidence level 3
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04 Chapter 1410 10/25/05 2:15 PM Page 30
Potentially mutagenic:3,28,29 Evidence level 3
Potentially carcinogenic:3,28,29 Evidence level 3
Although it is unclear if aloe components cross into breast milk, these compo-
nents are potentially genotoxic/mutagenic and carcinogenic to the nursing
infant.3,28,29
Avoid during lactation:3,31 Evidence level 4
A herbal safety and drug interaction compendium and a herbal medicine
compendium reported that aloe species should be avoided during lactation.3,31
Potential laxative:3,28 Evidence level 4
A herbal safety and drug interaction compendium and a herbal medicine
compendium reported that aloe species may cause diarrhea in the infant due to
aloe’s laxative effect.3,28
Topical
Use with caution: Evidence level 4
Infants nursing from a breast to which aloe has been topicallyapplied may be
susceptible to the same risks as if aloe components where ingested.
Contraindications2,3,26,30,32
Menstruation (especially menorrhagia and metrorrhagia)
Actively inflamed hemorrhoids
Intestinal obstruction
Acutely inflamed intestinal diseases (e.g. Crohn disease, ulcerative colitis,
appendicitis)
Abdominal pain of unknown origin
Kidney dysfunction
Children under 12 years of age
Caution
If used for more than 8–10 days
Postsurgical wounds33
Constituents
● Anthroquinone glycosides:3,30 aloin A, aloin B, aloinoside A, aloinoside B, 
7-hydroxyaloins, emodin
● Anthraquinone:34 aloe-emodin (1,8-dihydroxyanthraquinone)
● Aloresin A30
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Toxicology
● Aloe-emodin is potentially carcinogenic and genotoxic.29,35
● Acemannan exhibited significant cytotoxicity to human gingival fibroblasts;
however, in animals, oral administration of acemannan was found to be
safe.36–38
Pharmacology
● The anthraquinones (dried latex) in aloe exert a laxative and purgative effect
whereas aloe gel does not.3
● Aloe and aloe gum may have a hypoglycemic effect.11–13
● With husk of Isabgol, aloe significantly reduced total cholesterol, triglycer-
ides, fasting and postprandial blood sugar levels in diabetic patients, and
total lipids and increased high-density lipoprotein cholesterol.8
● Aloe vera gel has been shown to delay wound healing in women following
cesarean delivery or laparotomy.33
● Topical application – A. africana was found to have anti-arthritic and anti-
inflammatory effects.23
● Aloe vera gel was found to enhance phagocytosis in human bronchial
asthma.14
● Aloe vera gel was found to reduce pruritus by inhibiting thromboxane for-
mation in vivo, inactivating bradykinin in vitro, and inhibiting histamine.39
● Aloe vera gel may have anti-bacterial and anti-fungal effects.39
● The addition of aloe vera gel to a mild soap had a protective effect on the
skin of patients undergoing radiation therapy.19
Drug interactions
Anti-glycemic drugs11–13
Cardiac glycosides3
Diuretics2
Oral drugs31
Parts used3,30
Dried latex and gel from leaves
References
1. Jellin JM, Batz F, Hitchens K. Natural Medicines Comprehensive Database, 3rd ed.
Stockton, CA: Therapeutic Research Faculty, 2002:1530.
2. Blumenthal M, Busse WR, Goldberg A et al. The Complete German Commission E
Monographs: Therapeutic Guide to Herbal Medicines. Boston, MA: American
Botanical Council, 1998.
3. Newall CA, Anderson LA, Phillipson JD. Herbal Medicines: A Guide for Health-care
Professionals. London, UK: Pharmaceutical Press, 1996:296.
4. Wichtl M, Czygan FC, Frohne D et al. Herbal Drugs and Phytopharmaceuticals.
Stuttgart, DE: Medpharm-CRC, Press, 1994:566.
5. Odes HS, Madar Z. A double-blind trial of a celandin, aloevera and psyllium laxative
preparation in adult patients with constipation. Digestion 1991; 49:65–71.
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6. Chapman DD, Pittelli JJ. Double-blind comparison of alophen with its components
for cathartic effects. Curr Ther Res Clin Exp 1974; 16:817–820.
7. Lissoni P, Giani L, Zerbini S, Trabattoni P, Rovelli F. Biotherapy with the pineal
immunomodulating hormone melatonin versus melatonin plus aloe vera in untreatable
advanced solid neoplasms. Nat Immun 1998; 16:27–33.
8. Agarwal OP. Prevention of atheromatous heart disease. Angiology 1985;
36:485–492.
9. Atherton P. Aloe vera: magic or medicine? Nurs Stand 1998; 12:49–52, 54.
10. Dykman KD, Tone C, Ford C, Dykman RA. The effects of nutritional supplements
on the symptoms of fibromyalgia and chronic fatigue syndrome. Integr Physiol
Behav Sci 1998; 33:61–71.
11. Al-Awadi FM, Gumaa KA. Studies on the activity of individual plants of an anti-
diabetic plant mixture. Acta Diabetol Lat 1987; 24:37–41.
12. Al-Awadi FM, Khattar MA, Gumaa KA. On the mechanism of the hypoglycaemic
effect of a plant extract. Diabetologia 1985; 28:432–434.
13. Ghannam N, Kingston M, Al-Meshaal IA et al. The anti-diabetic activity of aloes:
preliminary clinical and experimental observations. Horm Res 1986; 24:288–294.
14. Shida T, Yagi A, Nishimura H, Nishioka I. Effect of Aloe extract on peripheral
phagocytosis in adult bronchial asthma. Planta Med 1985:273–275.
15. Syed TA, Ahmad SA, Holt AH et al. Management of psoriasis with Aloe vera extract
in a hydrophilic cream: a placebo-controlled, double-blind study. Trop Med Int
Health 1996; 1:505–509.
16. Syed TA, Afzal M, Ashfaq AS. Management of genital herpes in men with 0.5%
Aloe vera extract in a hydrophilic cream. A placebo-controlled double-blind study. 
J Derm Treatment 1997; 8:99–102.
17. Syed TA, Cheema KM, Ahmad SA. Aloe vera extract 0.5% in hydrophilic cream
versus aloe vera gel for the measurement of genital herpes in males. A placebo-
controlled, double-blind, comparative study. J Eur Acad Dermatol Venerol 1996;
7:294–295.
18. Vardy AD, Cohen AD, Tchetov T. A double-blind, placebo-controlled trial of Aloe
vera (A. barbadensis) emulsion in the treatment of seborrheic dermatitis. J Derm
Treatment 1999; 10:7–11.
19. Olsen DL, Raub WJ, Bradley C et al. The effect of aloe vera gel/mild soap versus
mild soap alone in preventing skin reactions in patients undergoing radiation therapy.
Oncol Nurs Forum 2001; 28:543–547.
20. West DP, Zhu YF. Evaluation of aloe vera gel gloves in the treatment of dry skin
associated with occupational exposure. Am J Infect Control 2003; 31:40–42.
21. Visuthikosol V, Chowchuen B, Sukwanarat Y, Sriurairatana S, Boonpucknavig V.
Effect of aloe vera gel to healing of burn wound a clinical and histologic study. J Med
Assoc Thai 1995; 78:403–409.
22. Poor MR, Hall JE, Poor AS. Reduction in the incidence of alveolar osteitis in
patients treated with the SaliCept patch, containing Acemannan hydrogel. J Oral
Maxillofac Surg 2002; 60:374–379.
23. Davis RH, Shapiro E, Agnew PS. Topical effect of aloe with ribonucleic acid and
vitamin C on adjuvant arthritis. J Am Podiatr Med Assoc 1985; 75:229–237.
24. Davis RH, Donato JJ, Hartman GM, Haas RC. Anti-inflammatory and wound heal-
ing activity of a growth substance in Aloe vera. J Am Podiatr Med Assoc 1994;
84:77–81.
25. Fulton JEJ. The stimulation of postdermabrasion wound healing with stabilized
aloe vera gel-polyethylene oxide dressing. J Dermatol Surg Oncol 1990; 16:460–467.
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26. Luyckx VA, Ballanti-ne R, Claeys M et al. Herbal remedy-associated acute renal
failure secondary to Cape aloes. Am J Kidney Dis 2002; 39:E13.
27. Farnsworth NR, Bingel AS, Cordell GA, Crane FA, Fong HH. Potential value of
plants as sources of new anti-fertility agents I. J Pharm Sci 1975; 64:535–598.
28. Brinker F. Herb Contraindications and Drug Interactions. Sandy, OR: Eclectic Medical
Publications, 2001:432.
29. Muller SO, Eckert I, Lutz WK, Stopper H. Genotoxicity of the laxative drug com-
ponents emodin, aloe-emodin and danthron in mammalian cells: topoisomerase II
mediated? Mutat Res 1996; 371:165–173.
30. Brinker F. The Toxicology of Botanical Medicines. Sandy, Oregon: Eclectic Medical
Publications, 2000:296.
31. Brinker F. Herb Contraindications and Drug Interactions. Sandy, OR: Eclectic Institute
Inc., 1997:146.
32. McGuffin M, Hobbs C, Upton R, Goldberg A. American Herbal Products
Association’s Botanical Safety Handbook. Boca Raton, FL: CRC Press, 1997:231.
33. Schmidt JM, Greenspoon JS. Aloe vera dermal wound gel is associated with a delay
in wound healing. Obstet Gynecol 1991; 78:115–117.
34. Muller-Jakic B, Breu W, Probstle A et al. In vitro inhibition of cyclooxygenase and
5-lipoxygenase by alkamides from Echinacea and Achillea species. Planta Med 1994;
60:37–40.
35. Westendorf J, Marquardt H, Poginsky B et al. Genotoxicity of naturally occurring
hydroxyanthraquinones. Mutat Res 1990; 240:1–12.
36. Fogleman RW, Shellenberger TE, Balmer MF, Carpenter RH, McAnalley BH. Sub-
chronic oral administration of acemannan in the rat and dog. Vet Hum Toxicol 1992;
34:144–147.